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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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BTI Filtration 27-Feb-07

Department of Health and Human Services' logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

 

4040 North Central Expressway
Dallas, Texas 75204-3145


February 27, 2007

Ref: 2007-DAL-WL-10

WARNING LETTER

CERTIFIED MAIL
RETURNED RECEIPT REQUESTED

Mrs. Crystal L. McKay, President
BTI Filtration
P.O. Box 93
Edmond, Oklahoma 73083

Dear Mrs. McKay:

During an inspection of your firm located at 7317 N. Classen Blvd., Oklahoma City, Oklahoma, on August 22 through 28, 2006, an investigator from the United States Food and Drug Administration (FDA) determined that your firm regenerates (manufactures) mixed bed deionization (DI) tanks and carbon tanks that are used to provide treated water to dilute dialysate for use in hemodialysis. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or any function of the body.

This inspection revealed that these devices are adulterated within-the meaning of section 501(h) of the Act (21 U.S.C. § 351(h)), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.

We received a response from you and Devin McKay, dated September 4, 2006, concerning our investigator's observations noted on the Form FDA 483, Inspectional Observations that was issued to you at the end of the inspection. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:

Quality System Violations

1.   Failure to validate and document with a high degree of assurance the results of a process that cannot be fully verified by subsequent inspection and test, and failure to have established procedures for such activities, as required by 21 CFR 820.75(a).

For example the manufacturing process for the regeneration of mixed bed DI tanks using the [redacted] Regeneration Plant has not been validated.  There is also no documentation indicating when the Regeneration Plant and the reverse osmosis water treatment system were installed and qualified for use. The Regeneration Plant includes a [redacted]

We have reviewed your response and have concluded that it is inadequate because you did not provide validation documentation for the manufacturing process described above.

2.  Failure to establish and maintain adequate process control procedures that describe any process controls necessary to ensure conformance to specifications, as required by 21 CFR 820.70(a). For example:

a.  Your Standard Operating Procedure (SOP) P9.01 Portable Tank Sanitization, effective April 3, 2000, requires that each empty DI tank be sanitized after the exhausted resin is dumped and before filling with regenerated resin.  SOPP19.25 Servicing, Description of Service, Portable Exchange Deionizer (PEDI) Tanks, effective December 19, 2002, states that “our P.E.D.I. tanks and service comply with ANSI/AAMI [redacted] and that "each tank shall be bleached with [redacted] with a [redacted] dwell time and rinsed with RO product water prior to re-bedding with regenerated P.E.D.I. resin."  Although your written procedures require sanitization of the DI tanks, your firm is not sanitizing these tanks.

Additionally, your firm does not have a complete copy of ANSI/AAMI [redacted] referred to in your SOP, for review and reference.

b. Your firm performs in-house microbiological testing [redacted] on the reverse osmosis water system use during the regeneration of resin using [redacted] Samplers.  There are no written procedures describing the specifications or the water, how the testing is to done, what you are testing for, and the frequency of the testing or action/alert levels.

We have reviewed your response and have concluded that it is inadequate because you did not provide process control procedures associated with the manufacturing of your regenerated mixed bed deionization (DI) tanks and carbon tank used in hemodialysis water purification systems for ensuring conformance to specifications.

3.   Failure to monitor and control process parameters and component and device characteristics during production, as required by 21 CFR 82(0(a)(2).

For example, your firm's SOP "P9.10 Reverse Osmosis RO) Water Treatment System" states that the RO system is to provide clean water for the processing of deionizer resins and that the RO system is monitored [redacted] and its monitoring results are to be documented on BTI Forms F9.04, F9.05, and F9.06. Your firm could not provide these forms or any other documentation of RO system monitoring results.

This issue was not included in the FDA 483 that was provided to you on August 28, 2006; however, we require that you address 21 CFR820.70(a)(2) in your response to this Warning Letter.

4.    Failure to establish and maintain procedures to prevent contamination of equipment or product by substances that could reasonably b expected to have an adverse effect on product quality, as required by 21 CFR820 70(e).  For example:

a.   Resins of returned mixed bed deionization tanks used or automobile washing and resins of returned mixed bed deionization tanks u for hemodialysis were dumped and commingled into one big batch of exhaust resins destined to be regenerated (recharged).  Your firm did not establish procedures for separating non-medical use resins from dialysis resins to prevent dialysis resins from being contaminated with potentially unwanted chemicals or toxins. Resin Batches 1747, 1752, 1755, 1761, and 1762 were reprocessed fort both automobile wash and medical use.

b. Your firm did not disinfect the DI and carbon tanks after lumping the exhausted resins or before filling the tanks with recharged resins in accordance with your SOP "Portable Exchange Deionizer Tanks, P19.25 Servicing," dated December 19, 2002.  The SOP make references to and states your firm is in compliance with the ANSI/AAMI [redacted] Standard.  The tanks were only rinsed with water.

This issue was not included in the FDA 483 that was provide to you on August 28, 2006; however, we require that you address 21 CFR 820.70(e) in your response to this Warning Letter.

5. Failure to ensure all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use, as required by 21 CFR 820.70(g).

For example, your firm could not locate the equipment operating manual for the regeneration plant (equipment) that was installed by [redacted] in [redacted] to ensure appropriate equipment maintenance as require by the original equipment manufacturer.

This issue was not included in the FDA 483 that was provided to you on August 28, 2006; however, we require that you address 21 CFR 820.70(g) in your response to this Warning Letter.

6. Failure to establish and maintain schedules for the adjustment, cleaning, and other maintenance of equipment to ensure that manufacturing specifications are met, as required by 21 CFR 820.70(g)(1).

For example, your firm provided the FDA investigator work orders of equipment maintenance activities that included [redacted] preventive maintenance (PM), replacement of the RO filter and post [redacted] filter and disinfection of the RO water storage tanks and loops, dated April 5 and 7, 2005; July 6, 2005 and May 8, 2006 for review.  However, your firm could not provide any documentation to ensure scheduled maintenance was performed from July 8, 2005 to May 8, 2006.

This issue was not included in the FDA 483 that was provide to you on August 28, 2006; however, we require that you address 21 CFR 820.70(g (1) in your response to this Warning Letter.

7.   Failure to establish and maintain acceptance procedures, including inspections, tests, or verification activities, for incoming product and for documenting the acceptance or rejection of the incoming product, as require by 21 CFR 820.80(b). For example:
 
a.   Your SOP P12.01 Inspection and Test Status, effective April 6, 2001, requires that the original marking on the chemicals not be obscured but does not define specifications for the acceptance or rejection of the chemicals or any components or raw materials.

b.   Your firm does not have any documentation of the manufacturer serial number and the internal serial number assigned by your firm to each of the empty DI and carbon tanks when received from the initial supplier, the acceptance activities performed when received, and the approval or rejection of these tanks.

c.  Your firm does not document the inspection of incoming exhausted DI and carbon tanks from your customers to determine suitability for continued use.

d.  For each lot of carbon received, your firm is checking the pH of the carbon to ensure that it does not contain [redacted] ash and documents this information on the Carbon Log. However, your firm does not have a procedure defining this testing or the criteria for acceptance or rejection of the carbon.

e.  Your firm has no written specifications for the regenerated resin, including the number of times the resin can be regenerated, the criteria for acceptance, the continued use of the resin and the chemical specifications for the resin.  Your firm had the regenerated resin analyzed on March 16, 2006, by a 3rd  party but could not explain nor interpret the 3rd party's test results for acceptance or rejection of the resin.

We have reviewed your response and have concluded that it is inadequate because you did not provide procedures that addressed all aspects of inspection and testing for acceptance or rejection of incoming product used in the manufacturing process of the regenerated mixed bed DI tanks and carbon tanks.

8.   Failure to establish and maintain acceptance procedures, where appropriate, for inspections, tests, or verification activities to ensure that specified requirements for in-process product are met, as required by 21 CFR 820.80(c).
 
For example, SOP P10.01 Inspection and Testing, effective April 6, 2001, states that there are certain tests and maintenance required for proper generation/regeneration of resin. The SOP states that the [redacted] and [redacted] used should be tested for specific gravity at every use and that if the specification is not met, then the [redacted] or the [redacted] is to be replaced. Your firm is not testing the [redacted] and [redacted] for specific gravity.

We have reviewed your response and have concluded that it is inadequate because you did not describe how you will ensure that adequate procedures for in-process acceptance of your regenerated mixed bed DI tanks and carbon tanks will be followed.

9.   Failure to establish and maintain adequate procedure acceptance for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria prior to releasing the devices for distribution, as required by 21 CFR 820.80(d). For example:

a.   SOP P19.25 Servicing Description of Service Portable Exchange Deionizer (PEDI) Tanks, effective December 19, 2002. states that “our P.E.D.I. tanks and service comply with ANSI/AAMI [redacted] and that "each tank shall be tested prior to delivery and shall test at no less than [redacted]’’  The operator of the Regeneration Plant said that he made sure the finished tank tested at greater than [redacted]. A review of the Resin/Batch logs from January 3, 2006 to July 31, 2006 showed that there were  approximately 527 regenerated DI tanks of various sizes that were designated for medical use on the log.  Although 171 of the 527 tanks did not meet the “no less than [redacted] requirement, they were released for distribution.

b. The operator of the Regeneration Plant and the person who performs finished product testing stated that if a regenerated DI tank initially has a low resistivity, they let the tank sit for a day or two and the resistivity sometimes goes up. They could not explain or provide a scientific rationale as to why this change in the resistivity value happens, but if resistivity is greater than [redacted] but less than [redacted] when the tank is re-tested, the tank is released.  This policy of re-testing tanks and accepting the second resistivity value for release of the DI tank is not defined in any procedure.

Examples of re-testing include the following:

  • On January 25, 2006, tank #187 had a resistivity of [redacted] The tank was retested on January 26, 2006, and the resistivity was [redacted]

  • On February 16, 2006, tank #336 had a resistivity of [redacted] The tank was retested on February 20, 2006, and the resistivity was [redacted]

  •   On February 20, 2006, tank #98 had a resistivity of [redacted] The tank was retested on February 22, 2006, and the resistivity was [redacted]

  • On July 12, 2006, tank #150 had a resistivity of [redacted] The tank was retested on July 14, 2006, and the resistivity was [redacted]

 
c.   Your firm does not have a written procedure indicating who is authorized to release finished product. The Resin/Batch and Carbon Logs are not signed to indicate release of regenerated mixed bed DI tanks and carbon tanks.

We have reviewed your response and have concluded that it is inadequate because you did not provide procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices will meet acceptance criteria prior to releasing them for distribution.

10.   Failure to establish and maintain procedures for rework, including retesting and reevaluation of the nonconforming product after rework, to ensure that the product meets its current approved specifications, as required by 21 FR 820.90(b)(2). For example:

a.    SOPP10.01 Inspection and Testing, effective April 6, 2001, states that "tanks are not reworked." Your firm does not always identify on the Resin/Batch Log when a regenerated DI tank is reworked (the regenerated resin is dumped back into the separator tank in the Regeneration Plant and goes through the regeneration process again), but there are several instances from January 3, 2006 to July 31, 2006 where regenerated DI tanks were reworked.
 

  • Tank #156 was filled with batch #1697 of regenerated resin on January 25, 2006 and had a resistivity of [redacted] The resin was dumped and regenerated again. The tank was filled with batch #1698 of regenerated resin on January 26, 2006 and had a resistivity of [redacted]

  • Tank #103 was filled with batch #1701 of regenerated resin on February 1, 2006 and had a resistivity of [redacted] The resin was dumped and regenerated again. The tank was filled with batch #1702 of regenerated resin on February 2, 2006 and had a resistivity of [redacted]

  • Tank #s 410, 413 & 414were filled with batch #1759 of regenerated resin on May 29, 2006. The resistivity was not recorded. The Resin/Batch Log indicates that these were the only tanks filled with this batch and that they were "DUMPED/REGEN". There is no explanation as to why the resin in these tanks was dumped and regenerated.

We have reviewed your response and have concluded that it is inadequate because you did not provide procedures to explain the entire rework process in detail, including procedures for retesting and reevaluation of the nonconforming product after rework, to ensure that the product will meet its current approved specifications.

11. Failure to establish and maintain the requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR820.50(a) .

For example, your firm has not defined the quality requirements to be met by your suppliers and has no written specifications for the empty DI and carbon tanks, carbon, resin [redacted] and [redacted] used in the manufacturing of the carbon tanks and regenerated mixed bed DI tanks.

We have reviewed your response and have concluded that it is inadequate because you did not provide documentation indicating the requirements, including quality requirements, that must be met by your suppliers, contractors, or consultants.

  • Failure to evaluate and select potential suppliers, contractors and consultants on the basis of their ability to meet specified requirements, including quality requirements, as required by 21 CFR 820.30(a)(1).

  For example, the SOP P 6.01 Purchasing and Vendor Evaluation, effective April 1, 2000, states that "vendors are selected based upon their ability to meet quality, price and delivery requirements. New vendors maybe used for [redacted] until one of the evaluation methods is accomplished. In no case may a vendor be used indefinitely without evaluation." It also states that "vendors will be evaluated routinely" and that "the review will be documented." There is no documentation that your firm has evaluated and approved any of your suppliers or contractors. Including the suppliers of the empty DI and carbon tanks, carbon, [redacted] and [redacted]

We have reviewed your response and have concluded that it is inadequate because you did not provide any documentation indicating that vendors are actively evaluated by your firm based on their ability to meet specified requirements.

13.   Failure to establish and maintain data that clearly describes or references the specified requirements, including quality requirements, for purchased or otherwise received product and services, as required by 21 CFR 820.50(b).

For example, your firm failed to maintain documentation of specifications and quality requirements for the empty deionizer tanks of various sizes, [redacted] activated carbon, and regenerated resins.

This issue was not included in the FDA 483 that was provided to you on August 28, 2006; however, we require that you address 21 CFR 820.50(b) in your response to this Warning Letter.

14.   Failure to ensure the device master record includes or refers to the location of the device specifications including appropriate drawings, composition, formulation, component specifications, and software specifications, as required by 21 CFR 820.181(a).

For example, your Device Master Record (DMR) does not include written specifications for the empty DI and carbon tanks, the resin, the carbon or regenerated/filled DI and carbon tanks.

We have reviewed your response and have concluded that it is inadequate because you did not provide documentation indicating that your firm's DMR has been modified to include, or refers to the location of, your device specifications including appropriate drawings, composition, formulation, component specifications, and software specifications for your regenerated mixed bed DI tanks and carbon tanks.
 
15.   Failure to maintain device master records that include, or refer to the location of, packaging and. labeling specifications, including methods an d processes used, as required by 21C FR 820.181(d).

For example, there is no documentation to show the current approved master label to be placed on all regenerated mixed bed DI and carbon tanks. Your firm has no written procedures for the labeling of the DI or carbon tanks.

We have reviewed your response and have concluded that it is inadequate because you did not provide documentation indicating that your firm's DMR for the regenerated mixed bed DI and carbon tanks has been modified to include, or refer to the location of, packaging and labeling specification documents, including methods and processes used.

16.    Failure to establish and maintain procedures for quality audits and conduct such audits to assure that the quality system is in compliance with established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR 820.22.

For example, your firm has not conducted any audits to detemine the effectiveness of your quality system and to assure your firm's compliance with the quality system requirements in 21 CFR Part 820.

We have reviewed your response and have concluded that it is inadequate because you did not provide quality audit procedures to ensure quality audits will be conducted in the future.

17. Failure to establish written procedures for identifying training needs and failure to ensure that all personnel are trained to adequately perform their assigned responsibilities, as required by 21 CFR 820.25(b).

For example, there is no documentation of any formal training provided to your firm's operator or another employee who sometimes works at the firm, both of whom are responsible for running the Regeneration Plant, for the regeneration and testing of the regenerated mixed bed DI tanks, and for filling the carbon tanks.

We have reviewed your response and have concluded that it is inadequate because you did not provide procedures for identifying training needs that will ensure that all personnel are trained to adequately perform their assigned responsibilities.

18.    Failure to establish and maintain procedures for identifying product during all stages of receipt, production, distribution, and installation to prevent mix-ups, as required by 21 CFR 820.60.

For example, the SOP 8.01 Product Identification and Traceability, effective April 3 , 2000, states that "the only item tracked from receipt is [redacted] Activated Carbon." The SOP does not require identification and traceability from receipt to production of new DI and carbon tanks exhausted DI and carbon tanks to be re-used [redacted] or the resin.

We have reviewed your response and have concluded that it is in adequate because you did not provide procedures for identifying your products during all the stages of receipt, production, distribution, and installation.

19.   Failure to establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, as required by 21 CFR 820.72(a).  For example:

a.   SOP P11.01 Calibration, effective November 10, 2000, states that your firm will maintain an Equipment List and include calibration and maintenance requirements for each piece of equipment on this list. However, your firm does not have an Equipment List, has not identified the equipment requiring calibration, and has not documented any justification as to why the equipment requires no calibration. Additionally, your firm does not include the specifications for the equipment requiring calibration or have a written calibration schedule identifying the frequency of calibration for the equipment.

b.   Your firm does not have any documentation to show that the scale used to weigh the regenerated DI tanks during filling, the pressure an temperature gauges used in the Regeneration Plant, and the resistivity meter used for finished product acceptance testing are routinely calibrated.

We have reviewed your response and have concluded that it is inadequate because you did not provide an equipment list, a written calibration schedule, procedures for identifying the frequency of calibration for the equipment, or other documentation that will ensure your equipment is routinely calibrated.

Medical Device Reporting (MDR)Violation

Our inspection also revealed that your regenerated mixed b DI and carbon tanks intended for use in hemodialysis are misbranded under section 2(t)(2) of the Act, 21 U.S.C. 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i,and 21 C.F.R. Part 803 - Medical Device Reporting (MDR) regulation. Significant deviations include, but are not limited to, the following:

1.   Failure to develop, maintain, and implement written MDR procedures, as required by 21 CFR 803.17. For example, your firm did not establish a procedure for MDR reporting.

We have reviewed your response and concluded that it is inadequate because you did not prepare and provide a copy of written MDR procedures for your firm.

Premarket Notification Violation

Our inspection also revealed that your regenerated mixed bed DI and carbon tanks that are intended for use in hemodialysis are adulterated under section 501(f)(1)(8) of the Act, 21 U.S.C. 351(f)(1)(B), because you do not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C.360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. 360j(g). The tanks are also misbranded under section 502(o) the Act, 24 U.S.C. 352(o), because you did not notify the agency of your intent to introduce the devices into commercial distribution, required by section 510(k) of the Act, 21 U.S.C. 360(k). For a device requiring premarket approval, the notification required by section 510(k) of the Act, 24 U.S.C. 360(k), is deemed satisfied when a PMA is pending before the agency. 21 C.F.R. 807.81(b). The kind of information you will need to submit in order to obtain approval or clearance for your devices is described on the Internet at http://www.fda.gov/cdrh/devadvice/3122.html.  The FDA will evaluate the information you submit and decide whether your devices maybe legally marketed.

Responding to This Warning Letter

You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation (21 CFR Part 820) deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.

Please notify this office in writing within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent the violations, or similar violations, from occurring again. Include documentation of the corrective action you have taken. If your planned corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.

Your response should be sent to Thao Ta, Compliance Offrce, Dallas District Office, Food and Drug Administration, HFR-SW140, 4040 N. Central Expressway, Suite 300, Dallas, Texas 75204. If you have any questions about the content of this letter please contact Mr. Ta at 214-253-5217.

Finally, you should know that this letter is not intended to be a all-inclusive list of the violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form FDA 483(FDA 483) issued at the closeout of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt actions to correct the violations and to bring your products into compliance.

Sincerely yours,

/S/

Michael A, Chappell
Dallas District Director
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